The matricellular protein decorin delivered intradermally with coacervate improves wound resolution in the CXCR3-deficient mouse model of hypertrophic scarring.
The matricellular protein decorin delivered intradermally with coacervate improves wound resolution in the CXCR3-deficient mouse model of hypertrophic scarring.
复制标题
基质细胞蛋白核心蛋白聚糖通过凝聚层皮内递送，改善了 CXCR3 缺陷小鼠肥厚性疤痕模型的伤口消退。
DOI：
10.1111/wrr.13017
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Wells,Alan
中科院分区：
文献类型：
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作者：
Sylakowski,Kyle;Hwang,MintaiPeter;Justin,Amritha;Whaley,Diana;Wang,Yadong;Wells,Alan
皮肤伤口愈合是修复的三个重叠阶段的复杂编排，包括许多细胞类型，信号级联和微环境修饰，以达到成功的解决方案。任何这些步骤的中断都会产生异常的愈合反应，导致溃疡或过度疤痕。很明显，细胞外基质及其相关成分是这一过程中的关键协调者。核心蛋白聚糖是其中一种重要的基质蛋白，它是一种富含亮氨酸的小蛋白聚糖（SLRP），可作为胶原纤维形成的调节剂和多种生长因子信号级联的非竞争性抑制剂。核心蛋白聚糖是组织替代阶段的促修复机制的必要关闭开关，并通过防止过度修复来限制肥厚性瘢痕的发生。我们通过在肥大性瘢痕小鼠模型中施用锚定在缓释凝聚层中的基质蛋白来研究核心蛋白聚糖作为治疗剂的用途。结果表明，与我们的仅凝聚物基线或HB-EGF治疗的对照小鼠相比，早期伤口愈合阶段测量显示性能差异很小。然而，在伤口愈合的消退阶段，核心蛋白聚糖治疗显著降低了皮肤厚度，增强了胶原蛋白排列，并改善了小鼠的整体伤口评分。因此，用核心蛋白聚糖处理的小鼠显示出更好的愈合结果，并且可以仅限制凝聚层和HB-EGF对照中的肥大性瘢痕形成表型。这些结果表明，核心蛋白聚糖可能是一个有前途的工具和替代疗法的患者遭受过度旺盛的基质沉积在伤口愈合。
Cutaneous wound healing is an intricate orchestration of three overlapping phases of repair that encompass numerous cell types, signalling cascades, and microenvironment modifications to reach a successful resolution. Disruption of any of these steps will create an abnormal healing response resulting in either ulceration or excessive scarring. It has become evident that the extracellular matrix and its associated components are key orchestrators during this process. One of these essential matrix proteins is decorin, a small leucine‐rich proteoglycan (SLRP) that acts as a regulator of collagen fibrillogenesis and a non‐competitive inhibitor of multiple growth factors signalling cascades. Decorin is a necessary shut‐off switch for the pro‐reparative mechanism of the tissue replacement phase and limits the occurrence of hypertrophic scarring by preventing excessive repair. We investigated the use of decorin as a therapeutic by administering the matrix protein anchored in a slow‐release coacervate in a hypertrophic scarring mouse model. The results show that early wound healing phase measurements exhibit little difference in performance compared to our coacervate‐only baseline or HB‐EGF‐treated control mice. However, during the resolution phase of wound healing, the decorin‐treatment significantly reduces cutaneous thickness, enhances collagen alignment, and improves overall wound scoring in the mice. Thus, mice treated with decorin display better healing outcomes and could limit the hypertrophic scarring phenotype in the coacervate only, and HB‐EGF controls. These results suggest that decorin may be a promising tool and alternative therapy for patients who suffer from over‐exuberant matrix deposition during wound healing.